Steve Noctor : Evolution and regulation of neural precursor cells in the developing vertebrate brain.

Work in rodent models shows that neural precursor cells (NPCs) in the subventricular zone of the prenatal forebrain produce excitatory cortical neurons destined for the cerebral cortex. A common pathway for neurogenic divisions in rodent cortex involves a two-step process by which Pax6-expressing radial glial cells divide in the ventricular zone to produce Tbr2-expressing NPCs that divide in the subventricular zone to produce cortical neurons. The origins of Tbr2-expressing NPCs are poorly understood, as are factors that regulate the output of NPCs. We investigated the evolutionary origin of Tbr2+ NPCs in the prenatal cerebral cortex by testing for the presence and distribution of Tbr2 cells in the prenatal cortex of reptiles and birds, and comparing it to known patterns in rodents and non-human primates. Recent work indicates that microglia colonize cortical proliferative zones in laboratory animals and regulate cell production by phagocytosing NPCs. We explored the evolution of this neuro-immune phenomenon by testing for the presence of microglia and characterizing the relationship between microglia and NPCs in each species.  We find that mitotic Tbr2-expressing cells are present in the prenatal cortex of reptiles and birds. Furthermore, we find that Tbr2-expressing cells are organized into an SVZ-like structure in some regions of the turtle forebrain, and in the cortices of chicken and dove. We also find that microglia colonize the proliferative zones and phagocytose Tbr2+ NPCs in each species examined in this study.  These results are consistent with the concept that neuro-immune regulation of cell genesis is common across vertebrates, and that Tbr2-expressing NPCs were present in the common ancestor of mammals and reptiles.